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KMID : 0624620200530110588
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BMB Reports
2020 Volume.53 No. 11 p.588 ~ p.593
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Activation of pannexin-1 mediates triglyceride-induced macrophage cell death
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Jung Byung-Chul
Kim Sung-Hoon
Lim Jae-Won
Kim Yoon-Suk
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Abstract
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The accumulation of triglycerides (TGs) in macrophages induces cell death, a risk factor in the pathogenesis of atherosclerosis. We had previously reported that TG-induced macrophage death is triggered by caspase-1 and -2, therefore we investigated the mechanism underlying this phenomenon. We found that potassium efflux is increased in TG-treated THP-1 macrophages and that the inhibition of potassium efflux blocks TG-induced cell death as well as caspase-1 and -2 activation. Furthermore, reducing ATP concentration (known to induce potassium efflux), restored cell viability and caspase-1 and -2 activity. The activation of pannexin-1 (a channel that releases ATP), was increased after TG treatment in THP-1 macrophages. Inhibition of pannexin-1 activity using its inhibitor, probenecid, recovered cell viability and blocked the activation of caspase-1 and -2 in TG-treated macrophages. These results suggest that TG-induced THP-1 macrophage cell death is induced via pannexin- 1 activation, which increases extracellular ATP, leading to an increase in potassium efflux.
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KEYWORD
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Cell death, Pannexin-1, Potassium efflux, THP-1 macrophages, Triglyceride (TG)
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